Atypical teratoid /rhabdoid tumor (AT/RT) of the
central nervous system is an extremely rare and aggressive tumor
of early childhood 1-6
7-11. The rarity
and the poor outcome with conventional infant brain tumor therapy
have resulted in a lack of clear treatment guidelines; therefore,
multiple approaches have been undertaken. It is for this reason
that a registry of patients with Central Nevous System (CNS) AT/RT,
their therapy, and their outcomes, was developed by Joanne Hilden
MD, Jaclyn A. Biegel PhD, and Jan Watterson BA. This registry was
to create an outcomes database that would track patients through
the disease process
.
AT/RT tumor was originally described as a variant of Wilms' tumor
with rhabdomyosarcomatous features 12.
Later the features differentiating AT/RT from Wilms' tumor were
clarified 13,14.
Reports of extra-renal rhabdoid tumors ensued with debate over a
different or common cell of origin 15.
The most frequent anatomic location for non-renal rhabdoid tumor
is the central nervous system (CNS). The designation of AT/RT refers
to the complex histologic features that may be present in these
tumors. The association of renal and CNS AT/RT 16
was consistent with cytogenetic studies that demonstrated abnormalities
of 22q11.2 in tumors from both sites17,18.
Molecular genetic studies have led to the identification of a rhabdoid
suppressor gene (INI1/hSNF5) at 22q11.2. Somatic mutations in this
gene predispose children to the development of AT/RT 19-24.
While this represents tremendous progress, not all mutations have
been discovered, as 25% of cases studied have no identified mutation
25. Further biologic
and molecular genetic studies are needed to aid both in clearer
diagnosis and in the hope of ultimately designing tumor-specific
therapy.
In terms of treatment outcomes, the early literature reflects a
time course from diagnosis to death of about 12 months with standard
therapy 5,6,26.
Subsequent reports document the use of more aggressive therapies
(including surgery, chemotherapy with or without stem cell support,
intrathecal chemotherapy, and early radiotherapy), with some prolongation
of the natural history of this tumor
1-3, 7, 27-31.
From these reports it is not possible to clarify the role of a specific
treatment method, as many different therapies were used. This fact
was made clear in a workshop co-sponsored by the Pediatric Brain
Tumor Foundation and the National Cancer Institute. Participants
concluded that despite multiple reports and information that significant
proportions of children younger than three years of age with malignant
brain tumors have AT/RTs, effective treatment strategies for these
tumors remain unclear and require further study. Until a nationwide
protocol for patients with AT/RTs is available, the AT/RT registry
should be maintained. Any information obtained from the registry
combined with information from prospective studies will facilitate
the development of optimal treatment approaches for children with
these tumors 7.
